Pathophysiology
Summary
While iodine deficiency is the leading global cause of hypothyroidism, it's not the only one. A deficiency in iodine results in insufficient thyroid hormone production, often evidenced by low serum T4 levels. Sometimes, this manifests as subclinical hypothyroidism, which can be asymptomatic with normal T4 levels. As a compensatory response, TSH is increased by the pituitary, stimulating the thyroid and causing follicular cell hypertrophy and hyperplasia. This leads to a diffuse, symmetrically enlarged goiter, known as endemic goiter.
Inconsistent iodine levels may trigger cycles of nodular formation & involution, ultimately resulting in an unevenly enlarged multinodular goiter. Interestingly, some nodules in a multinodular goiter can autonomously produce thyroid hormone without TSH, causing hyperthyroidism post-iodine replacement, or toxic multinodular goiter. Large goiters may bring additional complications, like tracheal compression causing dyspnea and stridor, or recurrent laryngeal nerve compression leading to hoarseness.
Riedel's thyroiditis is an autoimmune form of thyroiditis marked by severe fibrosis that obliterates the thyroid gland and extends to adjacent neck structures. It is often associated with systemic fibrosis, specifically in the context of IgG4-related systemic diseases like retroperitoneal fibrosis and autoimmune pancreatitis. It primarily presents with a hard, painless goiter. Diffuse fibrosis can compress critical neck structures, causing symptoms like dyspnea, stridor, dysphagia, or hoarseness. Hypothyroidism is a common progression, and intriguingly, about two-thirds of patients exhibit anti-thyroid autoantibodies similar to those in Hashimoto's thyroiditis. However, these autoantibodies are probably secondary consequences rather than causative agents.
Subacute granulomatous thyroiditis primarily affects middle-aged women and often follows a viral infection. It is characterized by a painful, inflamed goiter due to granulomatous inflammation with macrophages & helper T-cells. This inflammation can cause thyroid follicle rupture, leading to transient hyperthyroidism. A subsequent hypothyroid phase is common but usually asymptomatic, as most patients eventually revert to a euthyroid state.
Subacute lymphocytic thyroiditis, alternatively known as silent or painless thyroiditis, is considered a temporary form of chronic autoimmune thyroiditis, such as Hashimoto's. High levels of anti-thyroglobulin & anti-TPO antibodies are present early on. Initial inflammation damages the thyroid follicles, releasing stored thyroid hormone resulting in transient hyperthyroidism. This is typically followed by a hypothyroid phase and eventual return to a euthyroid state. Histology shows diffuse lymphocytic infiltrate and germinal center formation.
Other factors like lithium and amiodarone can adversely affect thyroid function. Lithium may induce hypothyroidism and goiter, although less commonly it can cause hyperthyroidism. Amiodarone, a class III antiarrhythmic, can impede T3 production and receptor binding or cause direct thyroid injury. Excessive iodine exposure can trigger the Wolff-Chaikoff effect, inhibiting thyroid peroxidase and leading to a hypothyroid state.
Lesson Outline
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FAQs
Iodine deficiency is the most common cause of hypothyroidism worldwide and can lead to a range of thyroid-related issues. A lack of iodine results in inadequate production of thyroid hormone, which can sometimes manifest as subclinical hypothyroidism with a normal T4 level. Over time, the pituitary gland releases increased amounts of TSH to stimulate the thyroid, causing hypertrophy and hyperplasia of follicular cells. This results in a diffuse, symmetrically enlarged goiter. In some instances, nodules in a multinodular goiter may autonomously produce thyroid hormone, leading to hyperthyroidism after iodine replacement.
Riedel's thyroiditis is an autoimmune condition characterized by intense fibrosis and inflammation of the thyroid gland, often leading to hypothyroidism. The condition is associated with systemic fibrosis and is often part of IgG4-related systemic diseases. The fibrosis can extend beyond the thyroid, affecting surrounding neck structures and causing symptoms like dyspnea, stridor, and hoarseness. Many cases of Riedel's thyroiditis progress to subclinical and overt hypothyroidism, although the presence of anti-thyroid autoantibodies is usually a secondary phenomenon.
Subacute granulomatous thyroiditis, commonly seen in middle-aged women following a viral infection, is characterized by diffuse granulomatous inflammation. This inflammation can cause thyroid follicles to rupture, leading to the release of stored thyroid hormone and transient hyperthyroidism. This is usually followed by a period of transient subclinical hypothyroidism. In most cases, the thyroid function eventually normalizes, returning to a euthyroid state.
Subacute lymphocytic thyroiditis is a transient condition that initially causes damage to thyroid follicles due to inflammation, leading to transient hyperthyroidism. This is often followed by a period of hypothyroidism before eventually returning to a euthyroid state. The condition is considered a transient variant of chronic autoimmune thyroiditis, such as Hashimoto's thyroiditis, and often presents with a painless goiter.
Drugs like lithium and amiodarone have been linked to hypothyroidism. Lithium can inhibit the release of thyroid hormones, leading to hypothyroidism and, less commonly, goiter formation. Amiodarone, a class III antiarrhythmic, can block the production of T3 and its receptors, and may also cause direct toxic injury to the thyroid. Excessive iodine intake can also inhibit thyroid peroxidase, preventing the formation of thyroid hormone and leading to hypothyroidism.
